Generation of Aβ peptides by endoproteolytic cleavage of β-amyloid precursor protein (APP) is a central event in the pathogenesis of Alzheimers disease (AD). Several APP mutations found in early-onset familial AD (FAD) cases, including the Swedish double mutation (Swe; K670N; M671L) or various presenilin mutations, increase Aβ production or favor the production of the more amyloidogenic Aβ42 species. These aggregate to form β-amyloid fibrils in plaques and perivascular deposits, the neuropathological hallmarks of AD [34]. Transgenic (tg) expression of mutated forms of human APP or altered secretases resulting in the formation of β-amyloid plaques in mice established the functional relevance of Aβ in the pathophysiology of the disease [11, 15, 21], and initial clinical proof of concept in AD patients who generated antibodies against β-amyloid in response to vaccination underscored the relevance of β-amyloid as a target for the therapy of AD [19]. The lack of a direct correlation between β-amyloid plaque load with the severity of disease symptoms in humans and some tg mice [1, 20, 22, 33], however, suggested the possibility of smaller oligomeric Aβ aggregates as primary toxic intermediates [14, 16, 36]. Several experiments demonstrated neurotoxic effects of such intermediates in vitro and in vivo [6, 8, 10, 25, 27, 35]. Intraneuronal deposits of Aβ were also observed in brains of AD patients, in particular in brain regions affected early in AD [13], but their relation to cognitive deficits in human patients is unclear. The majority of the FAD mutations in the APP gene are close to the Aβ domain although a few point-mutations are located within the Aβ sequence at positions 692-694. Interestingly, most of these mutations, including the Arctic mutation, cause severe cerebral amyloid angiopathy (CAA) [17, 18, 23, 24, 28], possibly related to less efficient clearance of Aβ across the blood-brain barrier (BBB) [9, 18, 30]. The Arctic mutation (E693G) at position 22 of the Aβ sequence alters the aggregation properties of Aβ by accelerating the formation of protofibrils [26, 32].